Identification of a cytotoxic form of dimeric interleukin-2 in murine tissues

Autor: William C. Grunwald Jr., Suzanne E. Clabaugh, Gino C. Liu, Lucile E. Wrenshall, John D. Miller, Prakash Arumugam, Deandra R. Smith, David R. Cool
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Cell Membrane Permeability
Physiology
medicine.medical_treatment
Receptor expression
lcsh:Medicine
Biochemistry
Mice
Animal Cells
Immune Physiology
Molecular Cell Biology
Morphogenesis
Cytotoxic T cell
Cell Cycle and Cell Division
Lymphocytes
lcsh:Science
Mice
Inbred BALB C
Multidisciplinary
Cell Death
Animal Models
3. Good health
Cell biology
Cytokine
Cell Processes
Cytokines
Anatomy
Cellular Types
Dimerization
Research Article
medicine.drug
Interleukin 2
Cell Physiology
Programmed cell death
Cell type
Membrane permeability
Immune Cells
Immunology
Blotting
Western
Myocytes
Smooth Muscle
Mouse Models
Biology
Research and Analysis Methods
Model Organisms
medicine
Animals
Heparanase
Molecular Biology Techniques
Sequencing Techniques
Molecular Biology
Cytokinesis
lcsh:R
Immunity
Biology and Life Sciences
Proteins
Epithelial Cells
Cell Biology
Molecular Development
Immune System
Spectrometry
Mass
Matrix-Assisted Laser Desorption-Ionization
Cardiovascular Anatomy
Interleukin-2
lcsh:Q
Developmental Biology
Zdroj: PLoS ONE, Vol 9, Iss 7, p e102191 (2014)
PLoS ONE
ISSN: 1932-6203
Popis: Interleukin-2 (IL-2) is a multi-faceted cytokine, known for promoting proliferation, survival, and cell death depending on the cell type and state. For example, IL-2 facilitates cell death only in activated T cells when antigen and IL-2 are abundant. The availability of IL-2 clearly impacts this process. Our laboratory recently demonstrated that IL-2 is retained in blood vessels by heparan sulfate, and that biologically active IL-2 is released from vessel tissue by heparanase. We now demonstrate that heparanase digestion also releases a dimeric form of IL-2 that is highly cytotoxic to cells expressing the IL-2 receptor. These cells include "traditional" IL-2 receptor-bearing cells such as lymphocytes, as well as those less well known for IL-2 receptor expression, such as epithelial and smooth muscle cells. The morphologic changes and rapid cell death induced by dimeric IL-2 imply that cell death is mediated by disruption of membrane permeability and subsequent necrosis. These findings suggest that IL-2 has a direct and unexpectedly broad influence on cellular homeostatic mechanisms in both immune and non-immune systems.
Databáze: OpenAIRE
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